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Abstract
Inflammation leads to chondrocyte senescence and cartilage degeneration, resulting in osteoarthritis (OA). Adipose‐derived stem cells (ADSCs) exert paracrine effects protecting chondrocytes from degenerative changes. However, the lack of optimum delivery systems for ADSCs limits its use in the clinic. The use of extracellular matrix based injectable hydrogels has gained increased attention due to their unique properties. In the present study, we developed hydrogels from amnion tissue as a delivery system for ADSCs. We investigated the potential of amnion hydrogel to maintain ADSC functions, the synergistic effect of AM with ADSC in preventing the catabolic responses of inflammation in stimulated chondrocytes. We also investigated the role of Wnt/β-catenin signaling pathway in IL-1β induced inflammation in chondrocytes and the ability of AM-ADSC to inhibit Wnt/β-catenin signaling. Our results showed that AM hydrogels supported cell viability, proliferation, and stemness. ADSCs, AM hydrogels and AM-ADSCs inhibited the catabolic responses of IL-1β and inhibited the Wnt/β-catenin signaling pathway, indicating possible involvement of Wnt/β-catenin signaling pathways in IL-1β induced inflammation. The results also showed that the synergistic effect of AM-ADSCs was more pronounced in preventing catabolic responses in activated chondrocytes. In conclusion, we showed that AM hydrogels can be used as a potential carrier for ADSCs, and can be developed as a potential therapeutic agent for treating OA.
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1 University of Connecticut Health, Connecticut Convergence Institute for Translation in Regenerative Engineering, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Department of Orthopaedic Surgery, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394)
2 University of Connecticut Health, Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Department of Orthopaedic Surgery, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut, Department of Chemical and Biomolecular Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915)
3 University of Connecticut Health, Connecticut Children’s Innovation Center, School of Medicine, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394)
4 University of Connecticut Health, Connecticut Convergence Institute for Translation in Regenerative Engineering, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Department of Orthopaedic Surgery, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut, Department of Biomedical Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Department of Materials Science and Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Institute of Materials Science, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915)
5 University of Connecticut Health, Connecticut Convergence Institute for Translation in Regenerative Engineering, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut Health, Department of Orthopaedic Surgery, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); University of Connecticut, Department of Chemical and Biomolecular Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Department of Biomedical Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Department of Materials Science and Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Institute of Materials Science, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut Health, Department of Craniofacial Sciences, School of Dental Medicine, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394)